Detection of adenovirus E1A DNA in pulmonary fibrosis using nested polymerase chain reaction

Abstract

The history of patients with idiopathic pulmonary fibrosis (IPF)shows that the disease may be preceded by a viral-like illness. Although viruses have not been demonstrated, it is possible that viruses were not detected in culture because they do not replicate during latency.We investigated the presence of adenovirus in IPF and interstitial pneumonia associated with collagen vascular disease (CVD-IP), using the nested polymerase chain reaction (PCR) and in situ hybridization (ISH) for the E1A region of the adenovirus genome. Studies were performed on lung tissues obtained by transbronchial lung biopsy from 19 patients with IPF, 10 patients with CVD-IP and, for comparison, from 20 patients with sarcoidosis.The E1A DNA was present in 3 out of 19 (16%) cases of IPF, in 5 of 10 (50%) cases of CVD-IP, and in 2 of 20 (10%) cases of sarcoidosis. The incidence of E1A DNA in CVD-IP was significantly higher than that in sarcoidosis (p<0.05). In patients with IPF and CVD-IP, E1A DNA was more prevalent in patients treated with corticosteroids (6 out of 9 cases; 67%) than in those without it (2 out of 20 cases; 10%) (p<0.01). ISH studies showed that 1 out of 8 cases of IPF and CVD-IP, in which E1A DNA was detected by PCR, was positive for E1A DNA.We conclude that adenovirus E1A is unlikely to be aetiologically involved in the pathogenesis of idiopathic pulmonary fibrosis or interstitial pneumonia associated with collagen vascular disease. However, a latent adenovirus infection may be reactivated or may newly infect the host following corticosteroid administration.

Experimental infections of humans with wild-type adenoviruses and with replication-competent adenovirus vectors: replication, safety, and transmission

“…59 A variable proportion of lung tissue specimens from patients with idiopathic pulmonary fibrosis, interstitial pneumonia associated with collagen vascular disease, and sarcoidosis were positive for Ad DNA, although there appeared to be no causal relationship. 60 Overall, the studies cited above suggest that Ad may persist and/or become latent in the tonsils, adenoids, or lungs of infected individuals.…”

Viruses: Cofactors in Idiopathic Pulmonary Fibrosis

“…Adenovirus is a double-stranded, 70-90 nm in diameter, nonenveloped DNA virus associated with many clinical conditions including interstitial lung disease [11,12]. Kuwano et al [12] investigated the presence of adenovirus in IPF and interstitial pneumonia associated with collagen vascular disease (CVD-IP).…”

“…Kuwano et al [12] investigated the presence of adenovirus in IPF and interstitial pneumonia associated with collagen vascular disease (CVD-IP). In patients with both IPF and CVD-IP, adenoviral DNA in lung tissue was measured in 67% of patients treated with corticosteroids compared with 10% in those patients not treated with corticosteroids.…”

Expanding the Spectrum of Particle-and Fiber-Associated Interstitial Lung Diseases

“…Several viruses have been implicated into the pathogenesis of IPF yet there is no clear evidence of viral etiology [12]. Viruses suggested to potentially have an etiologic relationship with IPF include EpsteinBarr virus (EBV), cytomegalovirus (CMV), influenza, hepatitis C virus, adenovirus, and human immunodeficiency virus type 1 (HIV-1) [13][14][15][16][17][18][19][20]. Hereditary factors may contribute to the risk of developing IPF but no specific genetic markers have been identified [21].…”